Our long term goal is to improve the success of revision joint replacements. In our original application we identified that a major deficit of revision implants is their diminished osteogenic performance. The objective for this proposal is to investigate autologous means for improving bony fixation in the revision implant. Specifically, we will study hypotheses addressing these three aims, (1) to improve access (of native growth factors, cells, marrow) to the implant interface by disrupting the sclerotic concentric bone (CB) barrier that forms during aseptic loosening, (2) to improve utilization and adhesion of native growth factors and cells via osteoconductive coatings encouraging bone growth directly on the implant surface, and (3) to augment the interface with local application of concentrated autologous growth factors. Aim 1: We will study improved access by determining if implant fixation parameters improve with a surgical procedure to disrupt the CB barrier. Aim 2: We will study hydroxyapatite (HA) and an immobilized RGD peptide surface (RGD) to determine if they improve utilization/adhesion as compared to titanium (Ti). Aim 3: We will study whether augmentation of the interface with autologous blood factors (concentrate of buffy coat in allograft carrier) improves interface fixation as compared to allograft alone, or to the ungrafted interface. We will use our experimental model of the primary and revision settings (established during the original proposal). This model uses the team's loaded micromotion device with over a decade of previous use (6.0mm diameter PMMA cylinder pistoning 500 microns for eight weeks with polyethylene particles, in 0.75mm gap) to engender a revision cavity with a bony and tissue response representative of an aseptically loosened human implant. At revision surgery, the PMMA implant is replaced with a prescribed implant/graft treatment (the primary site receives the same implant/graft treatment). Groupings are (a) stable, loaded Ti, HA and RGD implants, (b) with no graft, and allograft with or without growth factors, (c) in the primary setting, and the revision settings with and without disruption of the CB barrier. These 18 groups will be statistically compared with groups from the original proposal, to determine effectiveness, interactions and synergies of treatments. Outcome measures are histomorphometric (percent bone area and implant contact in zones, and connectivity) and mechanical (pushout strength, stiffness, energy, bone permeability). Also, the CB rim will be studied histomorphometrically and with an analytic mechanical model. The diverse set of unique competencies of our team, our established experimental model, and our long history of successful collaboration, bode well for our continuing investigations to improve the longevity of clinically vexing revision implants.